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31.
Changes of Respiratory Chain Activity in Mitochondrial and Synaptosomal Fractions Isolated from the Gerbil Brain After Graded Ischaemia 总被引:3,自引:1,他引:3
Kathryn L. Allen Angeles Almeida Timothy E. Bates John B. Clark 《Journal of neurochemistry》1995,64(5):2222-2229
Abstract: In this study we have examined (1) the integrated function of the mitochondrial respiratory chain by polarographic measurements and (2) the activities of the respiratory chain complexes I, II–III, and IV as well as the ATP synthase (complex V) in free mitochondria and synaptosomes isolated from gerbil brain, after a 30-min period of graded cerebral ischaemia. These data have been correlated with cerebral blood flow (CBF) values as measured by the hydrogen clearance technique. Integrated functioning of the mitochondrial respiratory chain, using both NAD-linked and FAD-linked substrates, was initially affected at CBF values of ∼35 ml 100 g−1 min−1 , and declined further as the CBF was reduced. The individual mitochondrial respiratory chain complexes, however, showed differences in sensitivity to graded cerebral ischaemia. Complex I activities decreased sharply at blood flows below ∼30 ml 100 g−1 min−1 (mitochondria and synaptosomes) and complex II–III activities decreased at blood flows below 20 ml 100 g−1 min−1 (mitochondria) and 35–30 ml 100 g−1 min−1 (synaptosomes). Activities declined further as CBF was reduced below these levels. Complex V activity was significantly affected only when the blood flow was reduced below 15–10 ml 100 g−1 min−1 (mitochondria and synaptosomes). In contrast, complex IV activity was unaffected by graded cerebral ischaemia, even at very low CBF levels. 相似文献
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35.
Tumor-induced endothelial cell activation: role of vascular endothelial growth factor 总被引:2,自引:0,他引:2
Castilla MA Neria F Renedo G Pereira DS González-Pacheco FR Jiménez S Tramón P Deudero JJ Arroyo MV Yagüe S Caramelo C 《American journal of physiology. Cell physiology》2004,286(5):C1170-C1176
Proangiogenic, proliferative effects of tumors have been extensively characterized in subconfluent endothelial cells (EC), but results in confluent, contact-inhibited EC are critically lacking. The present study examined the effect of tumor-conditioned medium (CM) of the malignant osteoblastic cell line MG63 on monolayer, quiescent bovine aorta EC. MG63-CM and MG63-CM + CoCl2 significantly increased EC survival in serum-starved conditions, without inducing EC proliferation. Furthermore, MG63-CM and MG63-CM + CoCl2, both containing high amounts of vascular endothelial growth factor (VEGF), induced relevant phenotypic changes in EC (all P < 0.01) involving increase of nucleoli/chromatin condensations, nucleus-to-cytosol ratio, capillary-like vacuolated structures, vessel-like acellular areas, migration through Matrigel, growth advantage in reseeding, and factor VIII content. All these actions were significantly inhibited by VEGF and VEGF receptor (VEGFR2) blockade. Of particular importance, a set of similar effects were detected in a human microvascular endothelial cell line (HMEC). With regard to gene expression, incubation with MG63-CM abolished endogenous VEGF mRNA and protein but induced a clear-cut increase in VEGFR2 mRNA expression in EC. In terms of mechanism, MG63-CM activates protein kinase B (PKB)/Akt, p44/p42-mitogen-activated protein kinase (MAPK)-mediated pathways, as suggested by both inhibition and phosphorylation experiments. In conclusion, tumor cells activate confluent, quiescent EC, promoting survival, phenotypic, and gene expression changes. Of importance, VEGF antagonism converts MG63-CM from protective to EC-damaging effects. vascular endothelial growth factor receptor 2; MG63-conditioned medium 相似文献
36.
Angeles Castillejo M Amiour N Dumas-Gaudot E Rubiales D Jorrín JV 《Phytochemistry》2004,65(12):1817-1828
Crenate broomrape (Orobanche crenata) is a parasitic plant that threatens legume production in Mediterranean areas. Pea (Pisum sativum) is severely affected, and only moderate levels of genetic resistance have so far been identified. In the present work we selected the most resistant accession available (Ps 624) and compared it with a susceptible (Messire) cultivar. Experiments were performed by using pot and Petri dish bioassays, showing little differences in the percentage of broomrape seed germination induced by both genotypes, but a significant hamper in the number of successfully installed tubercles and their developmental stage in the Ps 624 compared to Messire. The protein profile of healthy and infected P. sativum root tissue were analysed by two-dimensional electrophoresis. Approximately 500 individual protein spots could be detected on silver stained gels. At least 22 different protein spots differentiated control, non-infected, Messire and Ps 624 accessions. Some of them were identified by MALDI-TOF mass spectrometry and database searching as cysteine proteinase, beta-1,3-glucanase, endochitinase, profucosidase, and ABA-responsive protein. Both qualitative and quantitative differences have been found among infected and non-infected root extracts. Thus, in the infected susceptible Messire genotype 34 spots were decreased, one increased and three newly detected, while in Ps 624, 15 spots were increased, three decreased and one newly detected. In response to the inoculation, proteins that correspond to enzymes of the carbohydrate metabolism (fructokinase, fructose-bisphosphate aldolase), nitrogen metabolism (ferredoxin-NADP reductase) and mitochondrial electronic chain transport (alternative oxidase 2) decreased in the susceptible check, while proteins that correspond to enzymes of the nitrogen assimilation pathway (glutamine synthetase) or typical pathogen defence, PR proteins, including beta-1,3-glucanase and peroxidases, increased in Ps 624. Results are discussed in terms of changes in the carbohydrate and nitrogen metabolism an induction of defence proteins in response to broomrape parasitism. 相似文献
37.
Huerta JM González S Fernández S Patterson AM Lasheras C 《Free radical research》2004,38(11):1215-1221
Oxidative stress has been suggested as one of the physiopathologic conditions underlying the association of total plasma homocysteine (p-tHcy) with cardiovascular disease (CVD), but this hypothesis has not been validated in human epidemiological studies. We measured plasma and erythrocyte antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD), along with serum lipid-soluble antioxidants alpha-tocopherol, beta-carotene, lycopene and retinol, in a sample of 123 healthy elderly subjects (54 men, 69 women). Plasma malondialdehyde (p-MDA) was determined as a marker of lipid peroxidation, and p-tHcy was quantified by HPLC. No significant differences were found for p-MDA, GPx or SOD activities or serum antioxidant concentrations, in subjects with elevated p-tHcy (≥15 μmol/l) as compared to those with lower plasma homocysteine. Hyperhomocysteinemia did not lead to increased risk of having the highest p-MDA values, in either sex. We found no evidence that p-tHcy was associated with lipid peroxidation in this elderly human sample. Our results do not support the view that hyperhomocysteinemia would induce an adaptive response of antioxidant systems, either. More epidemiologic and clinical research is needed to clarify whether homocysteine promotes atherosclerosis by means of an oxidative stress mechanism. 相似文献
38.
Modamio-Høybjør S Moreno-Pelayo MA Mencía A del Castillo I Chardenoux S Armenta D Lathrop M Petit C Moreno F 《Human genetics》2003,112(1):24-28
Hereditary non-syndromic sensorineural hearing loss (NSSHL) is a genetically highly heterogeneous group of disorders. Autosomal dominant forms account for up to 20% of cases. To date, 39 loci have been identified by linkage analysis of affected families that segregate NSSHL forms in the autosomal dominant mode (DFNA). Investigation of a large Spanish pedigree with autosomal dominant inheritance of bilateral and progressive NSSHL of postlingual onset excluded linkage to known DFNA loci and, in a subsequent genome-wide scan, the disorder locus was mapped to 3q28-29. A maximum two-point LOD score of 4.36 at theta=0 was obtained for marker D3S1601. Haplotype analysis placed the novel locus, DFNA44, within a 3-cM genetic interval defined by markers D3S1314 and D3S2418. Heteroduplex analysis and DNA sequencing of coding regions and exon/intron boundaries of two genes (CLDN16 and FGF12) in this interval did not reveal disease-causing mutations. 相似文献
39.
Nitric oxide triggers the toxicity due to glutathione depletion in midbrain cultures through 12-lipoxygenase 总被引:5,自引:0,他引:5
Canals S Casarejos MJ de Bernardo S Rodríguez-Martín E Mena MA 《The Journal of biological chemistry》2003,278(24):21542-21549
Glutathione (GSH) depletion is the earliest biochemical alteration shown to date in brains of Parkinson's disease patients. However, data from animal models show that GSH depletion by itself is not sufficient to induce nigral degeneration. We have previously shown that non-toxic inhibition of GSH synthesis with l-buthionine-(S,R)-sulfoximine in primary midbrain cultures transforms a nitric oxide (NO) neurotrophic effect, selective for dopamine neurons, into a toxic effect with participation of guanylate cyclase (GC) and cGMP-dependent protein kinase (PKG) (Canals, S., Casarejos, M. J., de Bernardo, S., Rodríguez-Martín, E., and Mena, M. A. (2001) J. Neurochem. 79, 1183-1195). Here we demonstrate that arachidonic acid (AA) metabolism through the 12-lipoxygenase (12-LOX) pathway is also central for this GSH-NO interaction. LOX inhibitors (nordihydroguaiaretic acid and baicalein), but not cyclooxygenase (indomethacin) or epoxygenase (clotrimazole) ones, prevent cell death in the culture, even when added 10 h after NO treatment. Furthermore, the addition of AA to GSH-depleted cultures precipitates a cell death process that is indistinguishable from that initiated by NO in its morphology, time course, and 12-LOX, GC, and PKG dependence. The first AA metabolite through the 12-LOX enzyme, 12-hydroperoxyeicosatetraenoic acid, induces cell death in the culture, and its toxicity is greatly enhanced by GSH depletion. In addition we show that if GSH synthesis inhibition persists for up to 4 days without any additional treatment, it will induce a cell death process that also depends on 12-LOX, GC, and PKG activation. In this study, therefore, we show that the signaling pathway AA/12-LOX/12-HPETE/GC/PKG may be important in several pathologies in which GSH decrease has been documented, such as Parkinson's disease. The potentiating effect of NO over such a signaling pathway may be of relevance as part of the cascade of events leading to and sustaining nerve cell death. 相似文献
40.
de la Fuente MT Casanova B Cantero E Hernández del Cerro M Garcia-Marco J Silva A Garcia-Pardo A 《Biochemical and biophysical research communications》2003,311(3):708-712
We recently showed that alpha4beta1 integrin induces B-cell chronic lymphocytic leukemia (B-CLL) cell resistance to fludarabine-induced apoptosis via upregulation of Bcl-xL. We have now studied whether p53 was involved in this response. Cells from five B-CLL patients with wild-type p53 determined by DNA sequencing, or from the EHEB cell line, cultured on the alpha4beta1 ligand H/89 during fludarabine treatment, showed significantly higher viability (P相似文献